Clinical Features of Systemic Lupus Erythematosus

Clinical Features of Systemic Lupus Erythematosus

KEY POINTS

Systemic lupus erythematosus is the prototypic systemic autoimmune disease, characterized by diverse multi-system involvement and the production of an array of autoantibodies. Clinical features in individual patients can be quite variable and range from mild joint and skin involvement to severe, life-threatening internal organ disease. Criteria for the classification of systemic lupus erythematosus were initially developed by the American College of Rheumatology in nineteen seventy-one, revised in nineteen eighty-two, and revised for a second time in nineteen ninety-seven. A person must fulfill four of eleven criteria to be classified as systemic lupus erythematosus, all other reasonable diagnoses having been excluded. A patient does not have to manifest all four criteria simultaneously; the required four of eleven criteria can be fulfilled during a period of weeks or years. The American College of Rheumatology criteria were developed as a way to classify patients with systemic lupus erythematosus for the purpose of inclusion in clinical and epidemiologic studies. In clinical practice, these criteria are often cited to support a diagnosis of systemic lupus erythematosus. However, it should be emphasized that fulfillment of these classification criteria is not an absolute requirement for diagnosis. Rather, diagnosis typically rests on the judgment of an experienced clinician who recognizes a characteristic constellation of symptoms and signs in the setting of supportive serologic studies, after exclusion of alternative differential diagnostic possibilities. Despite widespread acceptance of the American College of Rheumatology criteria, several limitations affect their utility. The American College of Rheumatology criteria include only a subset of the various manifestations that might be present in a systemic lupus erythematosus patient. For example, despite the variety of neurologic syndromes that have been described in systemic lupus erythematosus, only seizures and psychosis are included in the American College of Rheumatology criteria. Proteinuria and urinary cellular casts are the only two renal criteria. Notably, a positive renal biopsy is not included in the criteria.

Against this background, the Systemic Lupus International Collaborating Clinics undertook an effort to revise the American College of Rheumatology criteria. Through review of more than seven hundred systemic lupus erythematosus and control patient scenarios and validation in a separate sample, seventeen elements were identified for inclusion into the revised criteria (eleven clinical and six immunologic). A patient is classified with systemic lupus erythematosus if he or she (one) has biopsy-proven lupus nephritis with a positive anti-nuclear antibody or anti-double-stranded deoxyribonucleic acid antibody or (two) fulfills four of the criteria, including at least one clinical criterion and one immunologic criterion. In contrast to the American College of Rheumatology criteria, the Systemic Lupus International Collaborating Clinics criteria would not allow a patient to be classified with systemic lupus erythematosus on the basis of clinical features alone. The revised criteria include more dermatologic and neurologic manifestations, as well as low complement levels and positive direct Coombs test in the absence of hemolytic anemia. Although the Systemic Lupus International Collaborating Clinics revision provides alternative criteria for use in research studies, it remains to be seen whether these criteria will ultimately replace the American College of Rheumatology criteria.

EPIDEMIOLOGY

Prevalence and incidence rates of systemic lupus erythematosus vary widely in the literature. Reported prevalence frequencies range from twenty to two hundred forty per one hundred thousand persons, and reported incidence rates range from one to ten per one hundred thousand person-years. This variation is partly the result of methodological differences between studies (e.g., different case definitions of systemic lupus erythematosus and methods of case ascertainment) and differing racial or ethnic compositions of the study populations. To determine more accurate and contemporary epidemiologic estimates for systemic lupus erythematosus in the United States, the Centers for Disease Control and Prevention funded five large-scale, population-based lupus registries to conduct extensive lupus surveillance. The completed Georgia and Michigan lupus registries, composed primarily of Caucasian and African-American patients, reported incidence rates of five point six per one hundred thousand person-years and prevalences of seventy-two point one to seventy-four point four per one hundred thousand persons. African-American women had the highest rates. Peak disease incidence occurred during reproductive years; African-Americans had a lower mean age of onset compared with Caucasians. Registries from California, New York, and the Indian Health Service are nearing completion and will provide robust incidence and prevalence estimates in the Asian, Hispanic, and Native-American populations. Previous studies suggest a higher prevalence of systemic lupus erythematosus in Asian and Hispanic populations.

Most patients with systemic lupus erythematosus are seen with their disease when they are between fifteen and sixty-four years old. Patients with pediatric-onset systemic lupus erythematosus (less than sixteen years old) are more likely to be African-American than patients with later-onset systemic lupus erythematosus. Systemic lupus erythematosus tends to be more severe in men and in pediatric patients. Late-onset systemic lupus erythematosus (greater than fifty years old) is characterized by a more insidious onset, with a higher occurrence of serositis and pulmonary involvement, and a lower incidence of malar rash, photosensitivity, alopecia, Raynaud's phenomenon, neuropsychiatric disease, and nephritis.